ABSTRACT
Ion channels play a central role in human physiology by helping regulate cellular ion homeostasis, shaping the electrical activity of nerve and muscle cells, and controlling the release of transmitters and hormones. The application of molecular biology and genetic approaches coupled with electrophysiology techniques has greatly facilitated the characterization of ion channel function. One important outcome of these advances has been the ability to understand a growing list of nervous system, cardiovascular, and metabolic disorders as specific defects in ion channel function [1-3]. The corollary of this observation is that modulation of ion channel activity represents an effective therapeutic strategy for a wide variety of disorders. Although small molecules and peptide toxins [4] that interact with ion channels have been known for some time, the technology for identifying new classes of lead compounds by high-throughput screening (HTS) has lagged behind the rapid advances in ion channel characterization. This review will summarize established as well as recently developed technology for configuring, validating, and running HTS campaigns for ion channel targets. However, continuing discoveries in ion channel function and the desire for further miniaturization and expedited sample screening means that utilizing the emerging technologies in fluorescent reporters and cell-based functional assays will be critical to the success of future lead discovery efforts.
